Central Journal of Clinical Nephrology and Research Review Article *Corresponding author Jose Rueda, MD, Division of Nephrology and Hypertension, Oregon Health & Science University, Mail Code: SJH6, 3181 S.W. Sam Jackson Park Road, Pheochromocytoma: A Single- Portland, OR 97239-309, Tel: 5034943442; Email: [email protected] Submitted: 18 February, 2021 Center Retrospective Review Accepted: 22 February, 2021 Benjamin K Elstrott1*, Lubna Khan2*, Divine Ribakare1,2, Published: 24 February, 2021 ISSN: 2379-0652 Abdallah Alali1,2, Ali Olyaei1,2,4, James Y Lim1,3, Jose F Rueda1,2 Copyright 1 Oregon Health & Science University, Portland © 2021 Elstrott BK, et al. 2Division of Nephrology and Hypertension, Portland OPEN ACCESS 3Department of Surgery, Portland 4Oregon State University, College of Pharmacy Keywords • Pheochromocytoma Abstract • Adrenal Gland Neoplasms • Incidental Findings Background: The presentation of modern pheochromocytoma is changing alongside advances in • Adrenal medulla medical practice. This retrospective review depicts the clinical presentation and biochemical properties of • Adrenalectomy pheochromocytomas as a function of size and cause for workup. Materials and Methods: Single-center retrospective chart review of imaging studies, biochemical testing results, and provider documentation written prior to surgical resections performed for pheochromocytoma between 1998 and 2018. Results: Forty-four patients were found to have 49 pheochromocytomas on pathology. The most common presentation was through incidental imaging findings of an adrenal mass (38.6%), followed by symptoms (34.1%), and then screening for known genetic risk (27.3%). Median unenhanced CT attenuation was 36 HU (range 17-85). Median pheochromocytoma size on imaging was 3.4 cm (range 1.0-12.2 cm). Median mass size in symptoms, incidental mass, and genetic risk groups were 4.1 cm, 3.4 cm, and 2.3 cm respectively (p = 0.090). Bilateral disease was more common in patients with known genetic mutations (41.7%, p = 0.040). Patients with tumors > 4 cm had higher total metanephrines in urine (p = 0.006) and more symptoms on average than those with tumors ≤ 4 cm (3.1 vs. 1.7 respectively, p = 0.017). Conclusion: In our single-center series, incidental adrenal masses and genetic testing were an increasingly common presentation leading to pheochromocytoma diagnosis on surgical pathology. Patients with known genetic syndromes more often had complex disease. Large tumors (>4cm) were associated with higher measurements of urine metanephrines and burdened patients with a greater number of symptoms. ABBREVIATIONS AND SYMBOLS PHEO: pheochromocytoma, PGL: paraganglioma, HU: necroticcross-sectional areas (8). imaging (6, 7). These tumors appear as contrast- CT: computed tomography, VHL: von enhancing, heterogenous masses on CT, often with cystic or Hippel-Lindau, NF1 MEN2: Multiple Pheochromocytoma is a rare cause of hypertension; EndocrineHoundsfield Neoplasia Units, 2, SDH B: Succinate Dehydrogenase Complex B. : Neurofibromatosis Type 1, hypertensive population, however, the prevalence approaches its prevalence is estimated between 0.01% to 0.2% in the INTRODUCTION 4% in populations with resistant hypertension (defined as Pheochromocytomas (PHEOs) are rare neuroendocrine amongstelevated bloodPHEO pressurepatients; despiteapproximately use of threehalf develop antihypertensive sustained drug classes) (9). The clinical pattern of hypertension is variable Extra-adrenal neuroendocrine tumors derived from sympathetic hypertension, another 45% experience paroxysmal hypertension, paragangliatumors arising are from known chromaffin as paraganglioma cells of the (PGL) adrenal and medulla occur less(1). frequently (2). PHEOs are generally well-vascularized and rarity, PHEO is important to suspect and diagnose in a timely and the remaining 5-15% remain normotensive (10). Despite its hypersecrete catecholamines which may cause symptoms such as headaches, excessive sweating, tachycardia, palpitations, and fashion not only because PHEOs harbor some malignant potential sometimes weight loss (3). As these symptoms are rather non- Whenbut also PHEO because is catecholaminesuspected, clinical secretion guidelines may be recommend associated measurementwith significant of cardiovascularurinary fractionated morbidity metanephrines and mortality or plasma (11). mortalityspecific, and (4, 5).as somePHEOs PHEOs are increasingly are asymptomatic, discovered there incidentally, can be a composingdelay in diagnosis nearly leading5% of to adrenal high cardiovascular incidentalomas morbidity found andon free metanephrines as the initial test to establish evidence of PHEO prior to imaging (12). Cite this article: Elstrott BK, Khan L, Ribakare D, Alali A, Olyaei A, et al. (2021) Pheochromocytoma: A Single-Center Retrospective Review. J Clin Nephrol Res 7(1): 1101. Elstrott BK, et al. (2021) Central The increasing affordability and accessibility of genetic testing combined with improved understanding of associated demonstrated in (Table 1) genetic mutations has expanded screening for PHEOs and remaining 11 patients had more complex presentations as familial PHEO syndromes which has led to earlier detection in . There were 26 right-sided PHEOs some populations (7). About 40% of PHEOs have been associated and 23 left-sided PHEOs. including patients whose initial workup was due to incidental with germline mutations such as Succinate Dehydrogenase Thirty-four patients (77.3%) reported at least one symptom, (SDH) complex mutations or as a part of other syndromes like findings or genetic risk. The most commonly reported signs and symptoms were refractory or paroxysmal hypertension (n= 24, Von Hippel-Lindau disease (VHL), Neurofibromatosis Type 1 Frequencies of reported symptoms are presented in (Figure 1). Screening for tumors in patients with known genetic mutations 54.5%), palpitations (n=20, 45.5%) and headache (n=15, 34.1%). results(NF1), andin earlierMultiple detection Endocrine and Neoplasia clinical manifestationsType 2 (MEN2) which (13). differ from those patients worked up due to symptoms (6,7). The median PHEO size on cross-sectional imaging was 3.4 The primary objective of our single-institutional study is to cm (range 1.0 cm to 12.2 cm). Unenhanced CT attenuation investigate differences in the clinical presentation, biochemical values were available for 20 PHEOs with a median value of 36 Hounsfield Units (HU) (range 17 to 85 HU). Complete imaging categories of patient presentations leading to discovery: reports were available for 19 patients; the three most common activity, and imaging findings of PHEOs based upon three descriptors used were contrast-enhancing (63%), cystic (26%), familial syndromes. and hyper vascular (23%). symptoms, incidental imaging finding, or screening for known METHODS Thirty-nine patients (88.6%) with PHEO had biochemistry We conducted a single-center retrospective study of all todata have available biochemically (24-h urine functional labs in tumorsn=24 [55%]; by urine plasma or plasmalabs in patients who underwent adrenalectomy for removal of PHEO sampling.n=32 [73%]). A weak Thirty-eight positive (97.4%) linear association of these patients between were the found total urine metanephrines and the size of pheochromocytomas is Health & Science University in Portland, Oregon. The patient illustrated in (Figure 2). databasebetween wasJanuary generated 1998 through aDecember query for 2018 PHEO at diagnosis Oregon codes. Patients were included in the study if an adrenalectomy postoperatively.In addition to Of the these, 12 patients 5 patients with were known diagnosed genetic withmutations, a new pathology report. Patients who received imaging or laboratory genetic syndrome.testing was The geneticperformed syndromes on 9 andadditional their frequencies patients testingwas performed for pheochromocytoma and a diagnosis ofwithout PHEO wassurgical confirmed intervention in the in our study population are shown in (Table 2). of surgery. This study was conducted with institutional review Comparing Pheochromocytoma Characteristics by boardwere excluded (IRB) approval; as well approvedas patients consent under thefrom age individual of 18 on subjectsthe date Reason for Workup was not indicated by the IRB for this retrospective study. Patients with PHEO were grouped and characterized by their Patients with synchronous bilateral pheochromocytoma were analyzed as a single event and a sum of longest mass diameters Table 1: was used in correlations of size to biochemical activity or symptoms. When redundant biochemical tests were documented PHEO DistributionPheochromocytoma Mass Distribution.No. of Patients No. of PHEOs for a patient, only the data from the latest pre-surgical test Isolated PHEO was included to be consistent for comparison across patients. Bilateral PHEOs 33 (75%) 33 (67%) Second PHEO in asynchronous 4 (9%) 8 (16%) metanephrines or urine fractionated or total metanephrines bilateral Biochemically functional tumors were defined as either plasma exceeding their respective reference ranges. PHEO with synchronous PGL 3 (7%) 3 (6%) Synchronous bilateral PHEO and All data analysis was performed using SPSS statistical 3 (7%) 3 (6%) software. Non-parametric variables were described by median PGL (IQR), with two-group comparisons made by Independent- Total 1 (2%)44 2 (4%)49 made by Independent-Samples Kruskal-Wallis ANOVA. A Table 2: Genetic Syndromes Present in Study Population. standardSamples Mann-Whitneyone-way ANOVA U Testwas andused three-group to analyze